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. 2012 Apr 1;72(7):1661-71.
doi: 10.1158/0008-5472.CAN-11-2957. Epub 2012 Feb 15.

Preclinical evaluation of TriMix and antigen mRNA-based antitumor therapy

Sandra Van Lint  1 , Cleo Goyvaerts, Sarah Maenhout, Lode Goethals, Aurélie Disy, Daphné Benteyn, Joeri Pen, Aude Bonehill, Carlo Heirman, Karine Breckpot, Kris Thielemans
Affiliations

Preclinical evaluation of TriMix and antigen mRNA-based antitumor therapy

Sandra Van Lint et al. Cancer Res. .

Abstract

The use of tumor-associated antigen (TAA) mRNA for therapeutic purposes is under active investigation. To be effective, mRNA vaccines need to deliver activation stimuli in addition to TAAs to dendritic cells (DC). In this study, we evaluated whether intranodal delivery of TAA mRNA together with TriMix, a mix of mRNA encoding CD40 ligand, constitutive active Toll-like receptor 4 and CD70, results in the in situ modification and maturation of DCs, hence, priming of TAA-specific T cells. We showed selective uptake and translation of mRNA in vivo by lymph node resident CD11c(+) cells. This process was hampered by codelivery of classical maturation stimuli but not by TriMix mRNA. Importantly, TriMix mRNA induced a T-cell-attracting and stimulatory environment, including recruitment of antigen-specific CD4(+) and CD8(+) T cells and CTLs against various TAAs. In several mouse tumor models, mRNA vaccination was as efficient in CTL induction and therapy response as vaccination with mRNA-electroporated DCs. Together, our findings suggest that intranodal administration of TAA mRNA together with mRNA encoding immunomodulating molecules is a promising vaccination strategy.

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